Health‐Protective and Adverse Effects of the Apolipoprotein E ɛ2 Allele in Older Men

Abstract

OBJECTIVES: To reexamine a health‐protective role of the common apolipoprotein E (APOE) polymorphism focusing on connections between the APOEɛ2—containing genotypes and impairments in instrumental activities of daily living (IADLs) in older (≥65) men and women and to examine how diagnosed coronary heart disease (CHD), Alzheimer's disease, colorectal cancer, macular degeneration, and atherosclerosis may mediate these connections. DESIGN: Retrospective cross‐sectional study. SETTING: The unique disability‐focused data from a genetic subsample of the 1999 National Long Term Care Survey linked with Medicare service use files. PARTICIPANTS: One thousand seven hundred thirty‐three genotyped individuals interviewed regarding IADL disabilities. MEASUREMENTS: Indicators of IADL impairments, five geriatric disorders, and ɛ2‐containing genotypes. RESULTS: The ɛ2/3 genotype is a major contributor to adverse associations between the ɛ2 allele and IADL disability in men (odds ratio (OR)=3.09, 95% confidence interval (CI)=1.53–6.26), although it provides significant protective effects for CHD (OR=0.55, 95% CI=0.33–0.92), whereas CHD is adversely associated with IADL disability (OR=2.18, 95% CI=1.28–3.72). Adjustment for five diseases does not significantly alter the adverse association between ɛ2‐containing genotypes and disability. Protective effects of the ɛ2/3 genotype for CHD (OR=0.52, 95% CI=0.27–0.99) and deleterious effects for IADLs (OR=3.50, 95% CI=1.71–7.14) for men hold in multivariate models with both these factors included. No significant associations between the ɛ2‐containing genotypes and IADL are found in women. CONCLUSION: The ɛ2 allele can play a dual role in men, protecting them against some health disorders, while promoting others. Strong adverse relationships with disability suggest that ɛ2‐containing genotypes can be unfavorable factors for the health and well‐being of aging men.

Angiotensin-converting enzyme (ACE) genotypes and disability in hospitalized older patients

“…Interestingly, the D allele of the ACE I/D polymorphism is often reported to be associated with cardiovascular diseases (Crisan and Carr 2000), and the presence of cardiovascular diseases can cause disability (Verbrugge and Jette 1994). Curiously, in a recent study, the same-type relationships were observed among cardiovascular diseases, apolipoprotein E, and instrumental activities of daily living (IADL) disability, and, similarly to the present study, those effects were found to be menspecific (Kulminski et al 2008). However, since we found a significant association between disability and ACE I/I genotype (i.e., a detrimental recessive model for I allele which corresponds to a protective dominant model for D allele), we investigated the same genetic model for the association with cardiovascular diseases considered as outcome, with no significant association between the ACE I/D polymorphism and cardiovascular diseases for all subjects and for men and females separately.…”

Trade-Off in the Effect of the APOE Gene on the Ages at Onset of Cardiocascular Disease and Cancer across Ages, Gender, and Human Generations

“…7 Furthermore, the same genes can confer risk for some traits but protect against the others, exhibiting so-called genetic trade-off. [16][17][18][19][20][21][22][23][24][25][26][27][28] Again, trade-off among endophenotypes can result in a tiny or no overall effect on an upstream phenotype. For example, Kulminski et al 17 show that the same allele of the apolipoprotein E (APOE) gene can confer risk for cardiovascular disease (CVD) but can protect against cancer that significantly alters estimates for life span.…”

Connections between apolipoprotein E genotypes and the development of cardiovascular diseases

“…További öt felmérés arra az eredményre jutott, hogy az e2-nek védő szerepe van a cardiovascularis betegségekkel szemben, vagy nem mutat velük összefüggést [35,44,45,46,47,48…”